Highly Tumorigenic Bay-Region Diol Epoxides from the Weak Carcinogen Benzo[c]Phenanthrene

  • D. M. Jerina
  • J. M. Sayer
  • H. Yagi
  • M. Croisy-Delcey
  • Y. Ittah
  • D. R. Thakker
  • A. W. Wood
  • R. L. Chang
  • W. Levin
  • A. H. Conney
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Four years ago at a symposium honoring the retirement of the late Professor R. T. Williams here at the University of Surrey, we presented a new theory which we hoped would be useful in explaining and predicting carcinogenicity for the polycyclic aromatic hydrocarbons (Jerina and Daly, 1976). This concept, the bay-region theory, proposed that diol epoxides of carcinogenic polycyclic aromatic hydrocarbons would have the highest biological activity when they were on angular benzo-rings and when the epoxide group formed part of a bay-region. Such bay-region diol epoxides were proposed as important ultimate carcinogens when metabolically formed from tumorigenic polycyclic hydrocarbons. The theory was based in part on the assumption that high chemical reactivity would be paralleled by high biological activity. Perturbational molecular orbital calculations by the method of Dewar (Dewar, 1969) provided a theoretical basis for the observed high chemical reactivity of bay-region diol epoxides relative to their non bay-region isomers (Jerina et al., 1976a). This concept is illustrated (Fig. 1) for the hydrocarbon benzo[a]anthracene. Thus for carcinogenic hydrocarbons with bay regions, benzo-ring arene oxides and their resultant trans dihydrodiols with bay-region double bonds were predicted to be proximate carcinogens, and bay-region diol epoxides were predicted to be ultimate carcinogens.

Keywords

Polycyclic Aromatic Hydrocarbon Epoxide Hydrolase High Biological Activity Polycyclic Hydrocarbon High Chemical Reactivity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • D. M. Jerina
    • 1
  • J. M. Sayer
    • 1
  • H. Yagi
    • 1
  • M. Croisy-Delcey
    • 1
  • Y. Ittah
    • 1
  • D. R. Thakker
    • 1
  • A. W. Wood
    • 2
  • R. L. Chang
    • 2
  • W. Levin
    • 2
  • A. H. Conney
    • 2
  1. 1.Laboratory of Bioorganic Chemistry, National Institute of Arthritis, Metabolism and Digestive DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Department of Biochemistry and Drug MetabolsimHoffmann-La Roche Inc.NutleyUSA

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